WO2017063448A1

WO2017063448A1 - Traditional chinese medicine composition for treating psoriasis

Info

Publication number: WO2017063448A1
Application number: PCT/CN2016/095963
Authority: WO
Inventors: 卢传坚; 赵瑞芝; 禤国维; 韩凌; 陈更新; 闫玉红; 刘丽娟
Original assignee: 广东省中医院
Priority date: 2015-10-15
Filing date: 2016-08-19
Publication date: 2017-04-20
Also published as: EP3363450B1; CN105213971B; EP3363450A4; CN105213971A; AU2016337828B2; EP3363450A1; AU2016337828A1; US20180289764A1

Abstract

A traditional Chinese medicine composition for treating psoriasis and applications thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5 to 15 parts of radix paeoniae rubra, 3 to 9 parts of curcuma zedoary, 10 to 20 parts of glabrous sarcandra herb, 10 to 20 parts of rhizoma smilacis glabrae, and 5 to 15 parts of dark plum. The traditional Chinese medicine composition can treat psoriasis and can reduce occurrence of complications thereof, such as cardiovascular events, psoriasis arthropathica and diabetes.

Description

Traditional Chinese medicine composition for treating psoriasis

Technical field

The present invention relates to a traditional Chinese medicine composition for treating skin diseases.

Background technique

Psoriasis is a genetically predisposed, systemic, chronic, inflammatory skin disease. It is typically characterized by recurrent scaly erythema or papules, with itching or pain, and with thin film and punctiform hemorrhage. Nail and joints are also affected. Its pathogenesis is not fully understood, mainly related to epidermal keratinocytes and immune dysfunction, involving complex immune and inflammatory responses. At present, there are 125 million psoriasis patients in the world, and the prevalence rate accounts for 3% of the world population, and it is increasing year by year. Worldwide, the highest prevalence of psoriasis is 8.2% in Norway. The total prevalence rate in China is 0.72%, and there are currently 10 million patients. According to the comparison of two large psoriasis epidemiological survey data conducted in 1984 and 2010, the incidence of psoriasis in China is still increasing. Psoriasis vulgaris accounts for 85-90%. Psoriasis can be divided into early and late onset according to the age of onset. The incidence of early onset psoriasis in China is 4.5 times higher than that of delayed onset psoriasis.

Psoriasis is indecent, causing patients to have a tendency to inferiority, while also affecting their employment and quality of life. Long-term treatment consumption not only brings serious economic and mental burden to patients, but also high morbidity and long-term treatment also cause a huge social burden.

Traditional treatment of psoriasis determines the drug to be used according to the severity of the disease. For mild patients, local treatment is mainly used. For moderate to severe patients, systemic treatment is used. Local treatment refers to topical use of corticosteroids, tar, eucalyptus, vitamin D analogues. He Zorrodin and so on. Its efficacy and side effects are shown in Table 1:

Table 1 Advantages and disadvantages of commonly used topical drugs for psoriasis

For patients with moderate to severe disease, systemic therapy is generally added on the basis of topical therapy. First-line drugs are mainly methotrexate The therapeutic effects and side effects of bismuth and cyclosporine, vitamin A (retinol) and its derivatives, fumarate, acitretin, etc. are shown in Table 2.

Table 2 Advantages and disadvantages of currently used psoriasis system treatment drugs

According to the European Psoriasis Foundation, only about 26% of patients are satisfied with traditional treatment. A survey in the UK found that 44% of patients prefer systemic therapy to more than topical administration. A survey of 17,994 patients by the European Psoriasis Association showed that only 27% of patients were satisfied with traditional treatment, and unsatisfactory items included severe side effects, time consumption, and low effectiveness of treatment. Therefore, the development of safe and effective psoriasis treatment drugs is still a hot spot in international drug development.

In the early stage, the applicant found a Chinese medicine compound for treating psoriasis in the clinic, and applied for and obtained the patent authorization (patent number ZL200910091066.5). Due to its medicinal taste and quality control, the applicant found that after several years of exploration, the applicant narrowed down. The prescription can also exert the effect of treating psoriasis when the dosage is increased at the same time. The second patent (201210183904.3) is applied, but the toxicity of the drug is also increased due to the increased dosage.

Summary of the invention

It is an object of the present invention to disclose a traditional Chinese medicine composition for treating psoriasis to overcome the deficiencies of the prior art and to meet the needs of the people.

The traditional Chinese medicine composition for treating psoriasis according to the present invention is prepared by using the following raw materials in parts by weight:

5 to 15 parts of red peony, 3 to 9 parts of medlar, 10 to 20 parts of swollen wind (nine teas), 10 to 20 parts of earthworms, ebony 5 to 15 servings;

Preferably, it is prepared in the following parts by weight of raw materials:

9 red peony, 6 medlar, 15 swollen wind (nine tea), 15 earthworms, 6 ebony;

Preparation:

The above medicinal materials were immersed in ten times weight of water for 1 hour, extracted twice, each time for 45 minutes, filtered, and the filtrate was concentrated to obtain a thick paste (specific gravity was 1.10 to 1.20), cooled to room temperature, and ethanol was added to an alcohol content of 70. %, placed for 24h, filtered, recovered ethanol, concentrated to obtain a thick paste (specific gravity measured is 1.30 ~ 1.40), which is the traditional Chinese medicine composition.

In vitro tests and clinical data show that the traditional Chinese medicine composition has remarkable therapeutic effects on psoriasis, psoriatic arthritis, rheumatoid arthritis or malignant tumor, and can be used for preparing psoriasis and silver shavings. A drug for arthritis, rheumatoid arthritis or malignancy, and less toxic.

The invention can be applied to a patient in need of treatment by oral administration, injection administration, sublingual administration, rectal administration, vaginal administration, transdermal administration, spray inhalation, and the dosage is 26-78 g/day, specifically The dosage is adjusted by the physician according to the condition;

Among them, the dose is based on raw herbs.

The invention also relates to a traditional Chinese medicine preparation comprising a therapeutically effective amount of said traditional Chinese medicine composition and a pharmaceutically acceptable carrier, said carrier comprising an excipient such as starch, dextrin, sodium carboxymethyl starch, Carboxymethyl cellulose, carboxypropyl cellulose, polyethylene glycol, glycerin, sorbitol, powdered sugar, wine, vinegar, lactose, compressible starch, microcrystalline cellulose, inorganic salts, mannitol, propylene glycol, Water, surfactant, benzoic acid, sorbic acid, paraben, sodium alginate, gum arabic, gelatin, methyl cellulose, sodium carboxymethyl cellulose, sodium salicylate, sodium chloride, etc., sweetness Such agents are stevioside, sucrose, aspartame, monosaccharide syrup, sodium saccharin, lactose, mannitol, sorbitol, acesulfame, and the like.

Preferably, the traditional Chinese medicine preparation is a tablet, a granule, a capsule, a pill, a pill, a powder, a ointment, a syrup, a plaster, a mixture, a wine, an elixir, a lozenge, a flow extract and an extract. , plaster, gel, ointment, tea, lotion, film, tincture, aerosol or spray;

The preparation method of the traditional Chinese medicine preparation is conventional, and the traditional Chinese medicine composition is mixed with a carrier, and then prepared into tablets, granules, capsules, pills, pills, powders by a method known in the art. , ointment, syrup, plaster, mixture, wine, tincture, lozenge, flow extract and extract, plaster, gel, ointment, tea, lotion, film, tincture, gas Aerosol or spray.

The beneficial effects of the invention are:

The therapeutic effect can be achieved in smaller doses. Compared with the 200910091966.5 patent, the invention has reduced medicinal taste and treatment The effect is enhanced; compared with the 201210183904.3 patent, the patent can exert better curative effect at a smaller dose, and the toxicity is significantly reduced; compared with the above two patents, the invention has a quick effect and can delay recurrence. It is more effective for psoriasis vulgaris (60% of PASI50), especially for early-onset patients, which can reduce the incidence of complications such as cardiovascular events, joint psoriasis, diabetes, etc. The incidence of symptoms is reduced by 20%), which can significantly improve the quality of life and the effect is better.

detailed description:

Example 1

Prescription 1:

Akasaka 9g, scorpion 6g, swollen wind (nine tea) 15g, bandit 15g, ebony 6g.

Preparation:

The above medicinal materials are immersed in 10 times water for 0.5 h, extracted twice, and the extract is filtered. The filtrate is concentrated to a relative density of 1.07-1.09, spray-dried, and the dried powder is mixed with starch, magnesium stearate, etc., and the tablet is obtained.

Example 2

Prescription 2

Red peony 15g, scorpion 3g, swollen wind (nine tea) 20g, bandit 10g, ebony 15g.

The above medicinal materials were soaked in 70% ethanol for 0.5 h, refluxed for 2 times, each time 0.5 h, filtered, and the filtrate was concentrated to a relative density of 1.13-1.15, sucrose powder was added, granulated, dried, and granulated to prepare a granule.

Example 3 Clinical Study Results:

1.1 diagnostic criteria

Western diagnostic criteria for psoriasis vulgaris: (Psoriasis treatment guidelines 2008 edition - recommended by the American Academy of Dermatology; Yang Guoliang, Wang Xiasheng. Modern Dermatology. Shanghai: Shanghai Medical University Press, 2005)

The basic damage begins with red papules or maculopapular rashes. From miliary to mung bean, it is covered with layers of silvery white scales. The scales are less acute and chronic damage is more. After the scale is scraped off, it is a red shiny film called a film phenomenon. Lightly scraping the film can cause scattered small bleeding spots, which are dew-like (Auspitz phenomenon). Occurs in the scalp, elbows, knees, joints and ankles. Dot-like depressions on the deck and oil drops under the deck. The mucosa has a clear red patch with no sharp edges. The lips can have silvery white scales. There are gray-yellow or white ring-shaped patches on the buccal mucosa and upper palate. Very few eye lesions occur, such as blepharitis and conjunctivitis.

Stigma vulgaris staging: (Yang Guoliang, Wang Xiasheng. Modern Dermatology. Shanghai: Shanghai Medical University Press, 2005)

Progression period: during the acute phase, there may be a homomorphic response.

Stable period: inflammation stops developing, skin lesions have no new hair, and are in a static state.

Regression period: damage is thinned, red is lightened, until the skin lesions disappear, leaving hypopigmentation or pigmentation spots.

Early hair, late hair diagnostic criteria:

Early onset (type I) patients before the age of 40, associated with human leukocyte antigen (HLA), especially HLA-Cw6, B57, DR7, the peak incidence is around 20 years old; late-onset (type II) patients after the onset of 40 years old , does not express HLA-DR7, overexpresses HLA-Cw2.

TCM syndrome differentiation standards: According to the "Chinese Medicine Industry Standards of the People's Republic of China" and "Principles of Clinical Research Guidelines for New Drugs of Traditional Chinese Medicine", dialectical criteria for the judgment of psoriasis TCM syndromes.

1.2 inclusion criteria

1 patients with stable, moderate, plaque, and >1 year of psoriasis.

2 age 18-65 years old.

3 The degree of skin lesion is 3 < PASI ≤ 10, and BSA ≤ 10%.

4 Those who signed the informed consent form.

1.3 exclusion criteria

1 The lesion is mainly in the form of spots, or the lesions are seen alone in the face, scalp, nails, wrinkles, glans, mucous membranes, and palmar palsy.

2 pregnant, lactating or planning pregnancy within 1 year.

3 Psychometric measurement scale SAS standard score > 50 points or SDS standard score > 53 points, or combined with other mental illness patients.

4 combined with circulatory system, respiratory system, digestive system, urinary system, endocrine system and hematopoietic system and other serious primary diseases, patients with uncontrollable medication, patients with tumors, serious infection, water, electrolytes and acid-base balance Disordered patients, and patients with calcium imbalance disorders.

5 Patients known to be allergic to the drugs used in this study.

6 Those who are participating in other drug clinical trials or who have participated in other clinical trials within 1 month.

In 72 weeks, he used hormones, retinoids and other external drugs or ultraviolet light therapy; those who received systemic therapy within 4 weeks; those who used biological agents within 12 weeks.

8 patients with acute progression of psoriasis and a tendency to have erythroderma.

9 patients who need to be treated with Western medicine.

1.4 Elimination of case criteria

1 After entering the group, it is found that the candidate is not eligible.

2 After entering the group, there is no data available.

2. Grouping and treatment

2.1 grouping

Qualified patients with psoriasis vulgaris were randomly divided into the patent group 2000910091066.5 test group, the patent 201210183904.3 test group, and the present invention group. Grouped by random assignment, the eligible cases were assigned to each group in a 1:1:1 ratio.

2.2 treatment

Referring to domestic and foreign literature and combined with the previous research results of the research group, the introduction period was 2 weeks, the treatment period was 12 weeks, and the follow-up period was 12 weeks.

3. Observing indicators and observation time

3.1 Baseline data

(1) Demographic indicators: date of birth, age, gender, ethnicity, nationality, marital status, education level, height, weight, occupation, long-term residence, etc.;

(2) Vital signs: body temperature, respiration, heart rate, blood pressure;

(3) History of allergies: history of drugs, food or contact allergies;

(4) History of disease and treatment: incidence of psoriasis, family history, past treatment history, and other diseases and treatment history;

(5) symptoms of Chinese medicine, pulse of the tongue;

(6) staging of psoriasis vulgaris: progress period, extinction period, stable period;

(7) Auxiliary examination: blood routine, urine routine, liver function, renal function, biochemistry, blood calcium, erythrocyte sedimentation rate, CRP, blood coagulation, blood lipids, electrocardiogram and systemic biological indicators; immunological indicators

(8) PASI, BSA, VAS, DLQI scale scores;

3.2 Clinical observation indicators in time

(1) PASI score, BSA, VAS: Recorded every 2 weeks every 2 weeks during the treatment period and during the follow-up period. During all observations and follow-up periods, the condition was aggravated and visited and recorded at any time.

(2) DLQI: Recorded every 4 weeks for all observations and follow-up periods.

(3) Skin lesion photography: Each visit is recorded by a doctor using a chromatic aberration-corrected digital photographic device to record the target lesion area and severity and tongue image.

(4) Concomitant medication: Record all patients' combined medications during the study period, and record the use of external medications and emergency medications. Record the cause, drug name, dosage, and duration of use of the combined drug.

(5) Adverse events and adverse reactions: All adverse events and adverse reactions occurred during the study period were recorded, and the treatment process was recorded.

(6) Drug distribution and recycling: record the number of drug visits per visit, and record the number of drugs left over from the previous visit.

3.3 Main outcome indicators:

(1) PASI-50

The proportion of patients with psoriatic lesion area and severity index (PASI) decreased by 50% before and after intervention, including 1 time every 2 weeks during the treatment period; once every 2 weeks during the follow-up period. The area and severity of lesions were recorded by a doctor using a chromatic aberration-corrected digital photographic apparatus, and compared with a standardized colorimetric plate of the color and infiltration degree of psoriatic plaque introduced in Japan to objectively evaluate PASI.

(2) Recurrence rate of psoriasis during treatment and follow-up

The recurrence was defined as: recurrence or exacerbation of the lesion in patients after improvement (PASI-50), and the PASI total score increased to 50% of the baseline value [Recommended by the American Dermatological Association Expert Group, Gordon K B, Feldman S R, Koo J Y M, et al. Definitions of Measures of Effect Duration for Psoriasis Treatments. Arch Dermatol, 2005, 141].

3.4 secondary outcome indicators:

(1) PASI score improvement rate:

PASI score improvement rate = (pre-intervention PASI score - post-intervention PASI score) / pre-intervention PASI score × 100%, PASI score observation and recording method is the same as before.

(2) PASI-75: The proportion of patients with psoriatic lesion area and severity index (PASI) decreased by 75% before and after intervention. The PASI score observation and recording method was the same as before.

(3) Skin surface area (BSA) of lesions: The pre-intervention, observation process, and follow-up procedure were evaluated. Among them, the treatment was recorded once a week during the treatment period and every 2 weeks during the follow-up period.

(4) Onset time: The onset time refers to the time when the patient reaches PASI-50 for the first time in the observation period, that is, the time interval from the start of treatment to the improvement of PASI score by 50%. If the PASI has not been improved by 50% during the patient observation period, It is considered invalid.

(5) Rebound rate: The rebound was defined as the recurrence and aggravation of the lesions of patients after improvement (achieving PASI-50), and the total score of PASI increased to 125% of the baseline value. Or converted to general pustular psoriasis and erythrodermic psoriasis.

4. Safety observation and evaluation

Laboratory safety testing programs include blood routine, urine routine, biochemistry, erythrocyte sedimentation rate, C-reactive protein, blood coagulation, blood lipids, and electrocardiogram (recorded once at week 0 and week 12). Systematic biological indicators (weeks 0 and 12) Once, at the same time, when the patient reached PASI-50, PASI-75 and recurrence and rebound, each record). Pay attention to the abnormal changes in laboratory test results, if necessary, review and further judge and evaluate its relevance to the study drug.

Severe adverse events or serious adverse reactions should be reported to the person in charge of the research site, the person in charge of the research group, and the contact person in a timely manner. All adverse events were analyzed and evaluated for association with study drugs.

4.1 Definition of adverse events

An adverse event is any adverse medical event that occurs in the subject in this clinical study, regardless of whether the event has a causal relationship with the study drug used above.

In the course of clinical research, the investigator still needs to record all adverse events observed, non-inducing questions, or complained by the subject, regardless of which medication group the adverse event should occur, and whether the adverse event is related to the treatment plan. At the same time, new diseases or exacerbations of the original symptoms during the study period should also be reported. Poor clinical intervention should not be recorded as an adverse event.

A total of 90 cases were included, 30 cases in each group. The administration methods are as follows:

The dose was 52 g/day, respectively, and the dose was based on raw herbs.

The above medicinal materials were extracted in accordance with Example 1 to prepare a standard decoction of 0.3 g/ml crude drug, which was administered twice a day.

The results are shown in Table 3.

Table 3 Clinical efficacy of the medicament of the invention for treating psoriasis

The three prescriptions did not undergo serious toxicity during the administration period.

Example 4

Effect of the medicament of the invention on the epidermis of the tail scale of mice:

Sixty KM mice qualified for adaptive feeding were selected, male and female, weighing 18g-25g. The mice were stratified by weight in Excel table, 6 mice per layer, and then the mice in each layer were randomly assigned. To each group, each group consisted of 10 groups, which were divided into 6 groups, namely normal control group, invention group, patent 200910091066.5 group, patent 201210183904.3 group, methotrexate tablet group and turmeric silver chip group. Each drug group was intragastrically administered with a volume of 20 mL·kg ^-1 ·d ^-1 every morning, once a day for 14 days, and the normal control group was given an equal volume of purified water. One hour after the last administration, the mice were sacrificed, and a strip of skin (about 1.0 cm × 0.2 cm) on the back of the root of the rat tail was taken and fixed with a 10% formaldehyde solution. Paraffin-embedded, HE stained, and the tail scales of each mouse were observed under an optical microscope. Where the scale epidermis between the two hair follicles has a granular layer arranged in a row, it is called a scale with a granular layer, and the number of scales having a granular layer per 100 scales is calculated, and the result is expressed as a percentage.

RESULTS: The granule cells of the tail squamous epithelium of the mouse were naturally absent, and only a small number of granulosa cells were present in the hair follicle, so the pathological features of keratosis of psoriasis could be simulated. Therefore, the rat tail epidermal model is a natural model and is currently recognized as one of the experimental psoriasis pathological models. Histopathological examination showed that there were fewer granule cells in the tail epidermis of the normal control group, and each drug group showed epidermal changes such as granular layer hyperplasia.

The data analysis showed that the present invention and the invention 201210183904.3 group, 2009100091066.5 group can significantly promote the formation of epidermal granule layer in the tail scale of mice, compared with the normal control group, the difference was significant (P<0.05 or P<0.01); methotrexate tablets Both the group and the turmeric group could significantly promote the formation of epidermal granule layer in the tail scale of mice, and the difference was significant compared with the normal control group (P<0.05 or P<0.01). The results are shown in Table 4.

Table 4 Effect of the present invention on the formation of epidermal granule layers in mouse tail scales (

n=10)

Note: ^* P < 0.05, ^** P < 0.01 compared with the normal control group.

The results showed no significant difference between the present invention group and the positive control drug, which was equal to or slightly superior to the efficacy of the first two patents, but the dose was greatly reduced.

Example 5

Effect of the medicament of the invention on propranolol-induced guinea pig psoriasis model:

Preparation of 5% propranolol hydrochloride emulsion: 5 g of propranolol hydrochloride was dissolved in 50% ethanol, 5 mL of 1,2-propanediol was added as a composite accelerator, and 5 g of PVPK30 was added as a film-forming material. 50% ethanol to 100 mL, made 5% propranolol hydrochloride emulsion, spare.

Eighty of the Hartley guinea pigs that were qualified for adaptive feeding were selected, male and female, weighing 200g to 250g. Randomly, 10 guinea pigs (male and female) were used as normal control group, no drug was given; the other 70 guinea pigs (male and female) were evenly spread on both ears with 5% propranolol hydrochloride emulsion (about 200 μL). The skin was applied twice a day for 4 weeks for modeling. Ten guinea pigs were sacrificed 4 weeks later to test whether the model was successful (in terms of ear skin thickness). Then, the remaining 60 guinea pigs which were molded for 4 weeks were layered by weight in an Excel spreadsheet, 6 guinea pigs per layer, and then guinea pigs of each layer were randomly assigned to each group, 10 mice in each group, which were divided into 6 groups, that is, The model control group, the present invention group, the invention 201210183904.3 group, the 2009100091066.5 group, the methotrexate tablet group and the turmeric silver chip group. Each drug group was intragastrically administered with a volume of 20 mL·kg ^-1 ·d ^-1 every morning, once a day for 10 days, and the normal control group and the model control group were given equal volume of purified water. One hour after the last administration, the guinea pigs were sacrificed, and the skin on the back of both ears was taken and fixed with a 10% formaldehyde solution. Paraffin-embedded, HE staining, observed under an optical microscope, several 10 high power fields, the thickness of the epidermis was measured with a microscopic measuring ruler, and the average value was taken; the auricle of the guinea pig was taken for pathological examination to observe the vasodilation, according to normal The light, medium and heavy levels are 0, 0.5, 1, 2, respectively.

RESULTS: Histopathological examination showed that the normal control group showed thinner stratum corneum, and the epidermal protrusion was not obvious. The model control group showed extensive hyperkeratosis and focal keratosis, and the granular layer became thin or disappeared. The layer is obviously hypertrophic, the epidermis is undulating, and the superficial dermal capillaries are dilated and congested. Data analysis showed that compared with the normal control group, the model control group significantly increased the epidermal thickness and dilated blood vessels in the guinea pig ears, and the difference was significant (P<0.01), indicating that the model of psoriatic pathological changes in the ears of guinea pigs was successful.

The results of histopathological examination showed that the invention, the invention 201210183904.3 group, the invention 200910091066.5 group, the methotrexate tablet group and the turmeric silver chip group showed obvious hyperkeratosis and parakeratosis, and the acanthosis was obviously thinned, and a small amount in the dermis. Capillary expansion. The data analysis showed that the present invention, the invention 201210183904.3 group, the invention 200910091066.5 group, the methotrexate tablet group and the turmeric silver chip group can significantly reduce the epidermal thickness of the guinea pig ear and reduce the vasodilation, compared with the model control group. The difference was significant (P<0.01); the methotrexate tablet group and the turmeric silver chip group could significantly reduce the epidermal thickness of the guinea pig ear and reduce the vasodilatation, and the model control group. The difference was significant (P < 0.01). It is shown that the present invention has an inhibitory effect on psoriatic pathological changes in the ear of guinea pigs. The results are shown in Table 5.

Table 5 Effect of the drug of the present invention on propranolol-induced guinea pig psoriasis model (

n=10)

Note: Compared with the normal control group, the model control group had ^△ P<0.05, ^△△ P<0.01; compared with the model control group, ^** P<0.01.

As can be seen from the above table, the present invention group is slightly superior to the positive control group, and is significantly superior to the patent 201210183904.3 group and the patent 200910091066.5 group.

Example 6

Comparison of toxicity between prescriptions:

(1) The experimental mice were fed for 3 days, and the rats were fasted for 16 hours before the experiment. The random number table method is divided into four groups, a blank group, a 200910091066.5 group, a patent 201210183904.3 group, and a group of the present invention, each group of 20, male and female.

(2) The blank group was intragastrically administered with normal saline, and the other three groups were administered according to the maximum tolerated dose (the most potable dose), which was converted into human clinical dose, 2 times a day, and only 1 day.

(3) The state of the mice after each gavage was observed, and the number of dead mice was counted.

(4) 48 h non-dead mice were observed for 2 weeks.

Experimental result

The maximum dose of the patent 200910091066.5 group was 79 times of the clinical dose. The first dose was administered, and the dose was the maximum dose (79 times). After the stomach was administered, the mice showed shrub, activity decreased, and tired, some The mice were breathing heavily. Within 15 minutes, 9 mice died, 3 males, 6 females, and the mice wheezed before death, bouncing, snout, and hind paws. Sharp black and purple.

Surviving mice returned to normal after 4 h.

The second time, the dose was added to the clinical 158 times, after the intragastric administration, within 5 minutes, 5 mice died, and after 24 hours, 5 died.

The maximum dose of the patent 201210183904.3 was 92 times of the clinically effective dose. After the first administration, the mice did not die, but there were symptoms such as shrugging, decreased activity, fatigue, and wheezing. After the second administration, Three mice died.

The maximum dose of the present invention is 195 times of the clinical dose. After the first gavage, the mice have symptoms such as burnout, decreased activity, and no death. After the second administration, the mice showed the performance after the first administration. The same, except for the reduction of activities, there is no other discomfort. The results are shown in Table 6.

Table 6 Comparison of toxicity between the drug of the present invention and the patent group of 2009. and 2012.

Claims

A traditional Chinese medicine composition for treating psoriasis, which is prepared by using the following raw materials in parts by weight:

5 to 15 parts of red peony, 3 to 9 parts of medlar, 10 to 20 parts of swollen wind, 10 to 20 parts of earthworms, and 5 to 15 parts of ebony.
A traditional Chinese medicine composition for treating psoriasis, which is prepared by using the following raw materials in parts by weight:

There are 9 red peony, 6 scorpion scorpions, 15 swollen winds, 15 earthworms and 6 ebony.
The use of a traditional Chinese medicine composition for preparing a medicament for treating psoriasis, characterized in that the traditional Chinese medicine composition is prepared by using the following raw materials in parts by weight:

5 to 15 parts of red peony, 3 to 9 parts of medlar, 10 to 20 parts of swollen wind, 10 to 20 parts of earthworms, and 5 to 15 parts of ebony.
The use of a traditional Chinese medicine composition for preparing a medicament for treating psoriasis, characterized in that the traditional Chinese medicine composition is prepared by using the following raw materials in parts by weight:

There are 9 red peony, 6 scorpion scorpions, 15 swollen winds, 15 earthworms and 6 ebony.
The use according to claim 3 or 4, wherein the medicament is administered by oral administration, injection administration, sublingual administration, rectal administration, vaginal administration, transdermal administration, spray inhalation route. For patients who need treatment.
The use according to claim 4 or 5, wherein the medicament comprises a therapeutically effective amount of the traditional Chinese medicine composition and a pharmaceutically acceptable carrier.
The application according to claim 6, wherein the medicine is a tablet, a granule, a capsule, a pill, a pill, a powder, a ointment, a syrup, a plaster, a mixture, a wine, an expectorant, Lozenges, flow extracts and extracts, plasters, gels, ointments, teas, lotions, lotions, elixirs, aerosols or sprays.